4. The presence of a family history of ocular diseases – especially glaucoma, but also including cataract, strabismus, amblyopia, and retinal problems – should be determined. Many glaucoma conditions are familial, and information about family members may aid diagnosis and treatment.

Furthermore, now that certain kinds of glaucoma have been related to specific gene abnormalities, elicitation of the family history and even pedigree may be very important for the patient and his or her siblings and offspring. Often, the patient may be aware of some familial eye problem but not be able to specifically identify it. Even in families with severe, blinding, genetic glaucoma, as much as onequarter of the relatives may be unaware of the condition.1

The ocular examination should include measurement of best visual acuity; an evaluation of the adnexa for exophthalmos, signs of trauma, or inflammation, and assessment of motility for signs of restriction or paresis.The pupil should be evaluated for size, shape, and reactivity. The slit lamp should be used for assessment of the cornea for epithelial, stromal, and endothelial abnormalities, and for anterior synechiae. The slit lamp should also be used to assess the iris for atrophy, growths, or blood vessels; the anterior chamber for depth and clarity, and the lens and vitreous for clarity.The IOP should be measured before dilation or gonioscopy. The examination should also include a careful evaluation of the retina and its vessels, the macula, and the optic nerve. The status of the optic nerve should be documented periodically, preferably by an objective method such as photography or another imaging technique. Careful descriptions or drawings are acceptable if photography or digital imaging is not available. The nerve fiber layer should be evaluated both for generalized thinning and for localized defects. Gonioscopy is indicated whenever the diagnosis of any kind of glaucoma is suspected. A visual field examination should also be undertaken either for baseline or for follow-up. Corneal thickness (pachymetry) should be ascertained in all open-angle glaucoma suspects and probably, at least once, in all glaucoma patients since thin corneas are a risk factor for progression to glaucoma from ocular hypertension and may help in determining target pressure ranges.2

Diagnosis

Several risk factors are known to contribute to the development of glaucoma, its progression or lack thereof, and its extent. The known factors include heredity, ethnicity, the size of the eye (small for angle closure, large for open angle), the presence or absence of systemic vascular disease, vasospastic disorders including migraine, and the size and shape of the optic cup (see Table 21-1). Although elevated IOP is a major risk factor, it is not the only one and is not, in and of itself, enough to account for all of the damage unless it is very elevated. As noted above, a thin cornea is a significant risk factor for development of open-angle glaucoma among ocular hypertensive eyes.2

People of black African descent have a much higher risk of developing open angle glaucoma and of becoming blind as a result of it.3–5 People of Hispanic descent also have a somewhat higher risk of open-angle glaucoma.6 Individuals descended from certain south-east Asian peoples, such as Chinese and Vietnamese, have a higher rate of angle-closure glaucoma than Caucasians; included in this group are some indigenous Americans.7,8

If glaucoma is thought of as a disease that damages the structural and/or functional integrity of the eye and can often be slowed or arrested by lowering IOP, then decisions are simplified. Those patients who have structural or functional damage either caused by pressure or affected by pressure should be treated. In most instances, the damage is fairly obvious, in the form of visual field loss, classic disc cupping, nerve fiber layer defects, corneal edema, arterial pulsations, or sometimes pain. Usually IOP is above the statistically normal range, so glaucoma is easy to diagnose. Once the disease is diagnosed, the decision to treat is simplified.

In other situations, things are not quite so simple. There may be questionable damage with normal pressure, or there may be elevated pressure without damage. These patients are glaucoma suspects and can be divided into four categories, depending on the level of IOP, the evidence of damage, and the presence of other risk factors.9

Identifying glaucoma suspects

The purpose of identifying someone as a glaucoma suspect is to be able to monitor that individual for the earliest sign of damage and, by intervening at that point, to prevent any visually significant damage from occurring in that person’s lifetime.This approach has the advantage of withholding treatment from those who may never need it.Thanks to the Ocular Hypertension Treatment Study (and later the European Glaucoma Prevention Study) we can now identify ocular hypertension patients who are at greatest risk of developing glaucoma and, perhaps, in these highest risk patients, begin

treatment even before serious damage has occurred to the optic nerve.2,10 Actual risk calculators have been worked out and vali-

dated to determine the relative risk of developing glaucoma from ocular hypertension.11,12

Although some patients have progressive glaucomatous damage with no recorded IOPs above 21 mmHg, other patients have IOPs frequently above 21 mmHg without exhibiting glaucomatous damage. The 21-mmHg mark remains useful for classifying glaucoma suspects for two reasons. First, 21 mmHg represents 2 standard deviations above the mean IOP of 16 mmHg in white populations. Pressure above this would occur in only 2.5% of normal cases if IOPs were indeed distributed normally in the population. Actually, the distribution of IOP is skewed to the right, so that 4–5% of ‘normal’ patients may have pressures higher than 21 mmHg. Although this is a small percentage of the normal patients, the actual number of patients with elevated IOP who never develop damage far exceeds the number of those who do develop damage. Therefore the chance of requiring treatment when only elevated IOP is present ( 30 mmHg), with no other risk factors, is probably less than 10%.13 Second, elevated pressure can cause glaucomatous damage. This is certainly true in experimental animals. The higher the pressure, the more rapidly the damage progresses. If the damage has not progressed too far, it can be arrested in many cases by adequate lowering of the IOP.  Thus elevated IOP is an important risk factor and must be taken seriously.

Anatomic signs may also make someone suspicious for glaucoma. Signs include the presence of narrow angles, an enlarged but not definitely pathologic optic cup, and thinning of or defects in the nerve fiber layer. Functional signs such as early but not definite visual field changes could also place someone in the suspect category. Color vision deficits may also herald the onset of glaucomatous damage. Finally, hereditary or genetic information – such as a

Box 21-1  Glaucoma suspect type I

Normal intraocular pressure, no damage

Strong family history of glaucoma Retinal vascular occlusion Exfoliative syndrome

Angle recession

Pigmentary dispersion syndrome Narrow angles

Uveitis

History of halos

Management: monitor periodically and inform patient of need for follow-up.

Box 21-2  Glaucoma suspect type II

Normal intraocular pressure, possible damage

Thin corneas Suspicious optic disc

Suspicious nerve fiber layer defects Suspicious visual field

Reduced psychophysical function

Management: confirm the finding by repeat testing if needed, as with suspicious visual fields. Demonstrate a normal variant, another cause of damage, or an elevated IOP expressed at other times. If the patient

demonstrates increased IOP, then treat for glaucoma. Otherwise, treat any other existing disease or conduct annual or semi-annual examinations depending on risk factors.

Box 21-3  Glaucoma suspect type III

High intraocular pressure, no damage

Management:

1.Pressure 35 mmHg (some authorities choose 30 mmHg): risk of damage is great. Treat.

2.Pressure 25–30 mmHg: treat if (1) other eye has damage; (2) patient is elderly or has siblings or parents with glaucoma; (3) patient has other risk factors; (4) patient has complicating ocular or vascular disease, or (5) there is poor patient follow-up or poor compliance or (6) thin corneas. If treatment is poorly tolerated, treatment may be stopped

and the patient observed at least every 4 months for progression of the disease.

3.Pressure 21–24 mmHg: treat if other eye has damage. Otherwise, observe. Some authorities would treat if the risk factor(s) above exist.

4.Pressure 25 mmHg and very narrow angles: consider laser iridotomy.

strong family history of glaucoma or possession of a gene associated with glaucoma, as well as other high-risk factors such as race or high myopia, even in the absence of elevated IOP or increased cupping – warrants closer observation than the general population. Table 21-1 lists the risk factors for primary open-angle glaucoma.

Damage to the optic nerve is central to the diagnosis of glaucoma. Damage to the functional or structural integrity of the eye that is

Box 21-4  Glaucoma suspect type IV

High intraocular pressure, possible damage

Peripheral anterior synechiae and narrow angles Notch or local rim narrowing of optic nerve Early arcuate scotoma or paracentral scotoma

Management: Generally, treat such eyes, especially if the other eye has damage, the patient has a strong family history, or the patient has a complicating ocular disease.

Box 21-5  Possible glaucomatous damage

Visual field

Generalized depression

Baring of blind spot

Nasal step 10°

Relative scotoma 5°

Statistical field loss index P 0.05–0.10

Visual function

Reduced color vision

Reduced temporal contrast sensitivity

Abnormal pattern electroretinogram

Optic nerve head

Cup-to-disc ratio 0.5

Asymmetry of disc cups 0.2 cup-to-disc ratio

Disc hemorrhage

Disc pit

Rim area 1.10 mm2

Vertically oval cup

Diffuse or localized nerve fiber layer defect

Chamber angle

Peripheral anterior synechiae

typical of glaucoma may be absent, questionably present, or present. If it is present, the patient either has or has had glaucoma or some disease that mimics it. If it is absent or questionably present, the patient may have glaucoma. Usually, the dilemma arises when trying to recognize early optic nerve or visual function damage typical of POAG.

If a patient is a glaucoma suspect, the ophthalmologist must decide whether to treat or to observe the patient. That decision usually is based on both the physician’s judgment of the amount of risk to the patient if left untreated and the patient’s anxiety about the condition (or about medications). Boxes 21-1 through 21-4 list some examples of various types of glaucoma suspects and their management. Signs indicative of disc or field damage are listed in Box 21-5.The purpose of observing the glaucoma suspect is to recognize any evidence of early damage. If damage progresses, then the presence of glaucoma (or other optic neuropathy) has been proven, and treatment must commence or be escalated.

Determining adequacy of treatment

If the patient is treated, how does the ophthalmologist determine whether adequate treatment has been provided? In the future it may be possible to make the optic nerve more resistant to either pressure-related damage or non-pressure-related damage, or to

treat directly the causes of non-pressure-related damage. Presently, our therapeutic tools only lower the patient’s IOP.  The real object, though, is to prevent or slow further structural or functional damage. Hence the first test of successful therapy is whether IOP has been lowered, but the ultimate test is whether progressive structural or functional damage has been prevented. Another issue of great importance is the patient’s quality of life. If the natural course of the disease has been for the cupping to progress but not to interfere with the patient’s important activities, then this must be weighed against any treatment plan that may seriously impair the patient’s quality of life – whether through functional interference or financial drain.

Intraocular pressure and its measurement are discussed in Chapter 4. One must remember, however, that it is difficult to know the patient’s true pressure range. In reality, IOP is measured infrequently – almost never at night or on Sunday, rarely after vigorous exercise or emotional upset, and never when the patient is sleeping. Thus the sample size of IOPs is quite small. For example, if pressure is measured for a period of 5 seconds once every 3 months, the sample is for only 5 seconds out of 7 776 000 seconds, giving a sample frequency of 0.0000643%.To make matters worse, the physician introduces bias into the sample by telling patients that they are going to be tested for the effect of the treatment prescribed by measuring their IOP when they return. Most patients want good test results, so

naturally they use the medication on the day they are tested – even though they may not use it regularly at other times.14,15

Theoretically, the effect a given treatment has on IOP when only one eye is treated can be determined with reasonable certainty (see Ch. 22). The other eye acts as a control, although a modest ‘crossover’ effect may be seen. While monocular treatment trial sounds like it should be an effective way of determining the effectiveness of treatment, it does not always work that way.16

Some medications may reach a peak effect in 2 hours after a single drop while others may take up to a month to reach full effect. The effects on IOP of the -adrenergic agonists, prostaglandins, topical carbonic anhydrase inhibitors, and cholinergic agents can usually be assessed within a few hours of using a drop although the prostaglandin analogs may take as much as a month or more to reach peak effect. -Blockers can produce a large immediate effect that diminishes over 4–6 weeks or, conversely, may require as much as a month for their full effect to develop.Adrenaline (epinephrine) derivatives, for example, may take as long as a month to show full effect, but their use is declining. Laser trabeculoplasty typically necessitates 4–5 weeks to reach maximum effect. Surgically lowering pressure rarely produces stabilized effects before 1 month, so it may take a month or more to determine the treatment’s effect on pressure.With medications, the physician can only assume that the pressure measured reflects what the medication can do to the IOP. It should never be assumed that the medications are being used regularly by the glaucoma patient.

A reasonable first goal in a younger patient with little damage is to lower the pressure at least 20% from the baseline IOP. Baseline pressure should be derived from at least two, and preferably more, measurements taken hours or days apart. Pressures can vary from hour to hour and day to day. The authors have seen patients with POAG undergoing baseline examinations before drug trials demonstrate a pressure variation of as much as 10 mmHg within 1 hour. Thus pressure can fluctuate markedly just as with measurement of any biologic function. If feasible, a trial in one eye is useful. If after the appropriate period there is little effect on IOP in the treated eye as compared with the untreated eye, then either the treatment

is not sufficient or the patient is not using it. Either way, the treatment is not successful.

It is not enough to lower IOP into the statistically normal range. Many patients continue to progress despite IOPs under 21 or 22 mmHg. The physician should set a target pressure for each patient.The target pressure is a ‘best guess’ level of IOP, below which further damage is unlikely to occur. The estimate is based on the initial level of IOP, degree of existing damage, age, and presence of other risk factors (see Ch. 22). Clinical experience and some statistical data support the concept that the more severe the existing optic nerve damage, the lower the IOP must be to prevent further deterioration.17–20 Thus a patient with early damage may tolerate a pressure around 20 mmHg, whereas a patient with advanced cupping and field loss may deteriorate unless the pressure is consistently below 16 mmHg. Moreover, 20 mmHg is considered ‘good’ control for a patient with early damage and initial pressures of 30 mmHg, but it is considered ‘poor’ control for a patient with a cup-to-disc ratio of 0.9 and advanced visual field loss and whose pressures have never exceeded 23 mmHg.The Advanced Glaucoma Intervention Study indicated that progression is not likely to occur if IOPs are always kept under 18 mmHg and the average hovers around 12 or 13 mmHg.21 The more risk factors and the greater the damage at the time of diagnosis, the lower the target pressure should be set. As time goes on, the target pressure should be reassessed and lowered if progression of damage occurs.

Treatment follow-up

The initial efficacy of therapy is determined by its effect on IOP, but long-term efficacy must be determined by analysis of damage. Therefore it is essential to have good baseline studies of the factors to be followed, which most often are the visual field and the optic nerve head (Table 21-1). Careful and rigorous documentation of the initial status of these factors is essential to ensure accurate decisions regarding future therapy.Analysis of both is discussed in detail in subsequent chapters.

Once a therapy has been determined effective, how should the treatment be followed? Determining follow-up procedures depends on two factors – amount of damage and adequacy of pressure control. Guidelines for pressure control for long-term management of chronic open-angle glaucoma are presented in Table 21-2. These guidelines may not be applicable in all situations, and the physician must individualize each case. One must also remember that the IOP measured in the office is a minute sample size of the patient’s

Table 21-1  Levels of damage

Table 21-2  Guidelines for level of intraocular pressure (mmHg) control related to damage level*

*These guidelines are only estimates. The target pressures should be individualized. The more advanced the glaucoma, the older the patient, the greater the number of risk factors, and the greater the vascular component, the lower the target pressure should be. The more advanced the damage and the poorer the control, the more frequent the re-evaluations must be. The fewer the number of risk factors and the less advanced the glaucoma, the more tolerant the optic nerve is likely to be of slightly elevated pressures. The better the control, the earlier the disease, and the fewer the number of risk factors, the less frequently the patient can be evaluated.

pressure; the ultimate decisions affecting therapy rest on changes in the visual field or the optic nerve head.

Documentation of progress

Like any psychophysical test, visual fields fluctuate. Computerized perimetry quantifies this fluctuation, thereby offering advantages over manual techniques. Recognition of change in the visual field, however, is confounded by this fluctuation.To minimize confusion introduced by this fluctuation, a newly diagnosed glaucoma patient may require two or three field examinations in the first year of diagnosis to establish a firm baseline for future comparison. This concept is discussed in Chapter 9.

Photographs or other forms of imaging of the optic nerve are also invaluable in evaluating progression of the disease and should be taken at the initial examination and subsequently whenever change is suspected. Careful examination of the disc should be performed at least every 6 months and more frequently if the pressure is uncontrolled. Repeat photographs or imaging should occur every 1–3 years even if there does not appear to be any clinical change. Usually photographs or imaging techniques detect subtle changes before the clinician can do so. The frequency of IOP measurements should be related to the adequacy of control of the disease. If the disease has been stable for several years and the pressure constant, then follow-up examinations can be performed safely 1–3 times a year. If the pressure is high or the disease is newly diagnosed and the physician is unsure of the response to medications, visits may be scheduled weekly or monthly until the physician is certain that rapid worsening of damage will not occur. If the pressure is very high then more frequent visits may be necessary.

Pressure measurements are at best a guideline for the effectiveness of therapy. It is necessary to measure the visual field and/or fundus to know if the disease is truly controlled. In advanced disease with fixation threatened, it is reasonable to perform visual field examinations every 6 months or so, perhaps using a high-resolution test pattern such as a 10–2, to detect the earliest sign of progression and start more aggressive therapy. Indeed, examinations less often

Table 21-3  Recommended frequency of visual field evaluation

Modified from American Academy of Ophthalmology: Primary openangle glaucoma, preferred practice pattern, San Francisco, American Academy of Ophthalmology, 1996.

N/A, Not applicable.

than this make it difficult, if not impossible, to distinguish normal fluctuation of the test from pathologic change. In a patient with less severe damage whose IOP is well controlled, field examination once a year or so is sufficient. In glaucoma suspects, or in glaucoma patients with no visual field loss and well-controlled pressures, field examinations may be performed annually. One suggested schedule for the frequency of visual field follow-up is proposed by the American Academy of Ophthalmology’s Preferred Practice Pattern for primary open-angle glaucoma (Table 21-3).

Optic nerve photography as well as newer tests such as laserassisted imaging and computer analysis of the nerve fiber layer or optic nerve head also may be helpful in recognizing progression of the disease.The clinician can still provide sensitive and accurate determination of progression using a carefully performed clinical field examination supplemented with a clinical and photographic evaluation of the nerve head.

Patient education

Because glaucoma is a chronic, lifelong condition with few debilitating symptoms, patient cooperation with follow-up and treatment is crucial to the success of management. Patients must be educated about their disease initially, then frequently during follow-up. Poor compliance with treatment is correlated with poor understanding of glaucoma and its long-term dangers.15 Even with good patient education, compliance may be inadequate in as high as onethird of patients.15 Many brochures (examples include those from the Glaucoma Research Foundation, the American Academy of Ophthalmology, Prevent Blindness America and several commercial publishers) are now available that help the physician to describe glaucoma, treatment alternatives, and the advantages and disadvantages of such alternatives. Some of these organizations provide an ‘800’ number where questions about glaucoma or its treatment can be answered. Patients can also find information on the Internet, but the reliability of that information cannot always be confirmed.The physician should supplement any outside information with open discussion. Glaucoma support groups, where patients share their experiences, exist in some places and may be helpful.

Questions should be welcome. Many patients need constant encouragement and re-education over the years. Patients should also